Exome-Driven Characterization of the Cancer Cell Lines at the Proteome Level: The NCI-60 Case Study

Cancer genome deviates significantly
from the reference human genome,
and thus a search against standard genome databases in cancer cell
proteomics fails to identify cancer-specific protein variants. The
goal of this Article is to combine high-throughput exome data [Abaan
et al. Cancer Res. 2013] and shotgun proteomics analysis
[Modhaddas Gholami et al. Cell Rep. 2013] for cancer
cell lines from NCI-60 panel to demonstrate further that the cell
lines can be effectively recognized using identified variant peptides.
To achieve this goal, we generated a database containing mutant protein
sequences of NCI-60 panel of cell lines. The proteome data were searched
using Mascot and X!Tandem search engines against databases of both
reference and mutant protein sequences. The identification quality
was further controlled by calculating a fraction of variant peptides
encoded by the own exome sequence for each cell line. We found that
up to 92.2% peptides identified by both search engines are encoded
by the own exome. Further, we used the identified variant peptides
for cell line recognition. The results of the study demonstrate that
proteome data supported by exome sequence information can be effectively
used for distinguishing between different types of cancer cell lines.